The proposed research will evaluate treatment of self-injurious behavior of 24 mentally retarded adults in institutional settings using the opiate antagonist naltrexone alone and with the alpha adrenergic agonist clonidine. A double-blind, within-subject dosage comparison (placebo, 50 and 100 mg/day naltrexone) and across group comparison of naltrexone alone versus naltrexone plus clonidine (0.3 mg/day) will be made. Recent data reveal some self-injury may be responsive to opiate antagonists, suggesting the endorphin/enkephalin ligand system may be involved in maintaining self-injury in some individuals. It is hypothesized some mentally retarded individuals initially injure themselves accidentally, causing release of endogeneous opioid ligand. It is known that enkephalins serve as powerful rewards, substituting for opiates such as morphine in laboratory self- administration arrangements. After repeated self-injury, with associated endorphin/enkephalin release and occupation of the opiate receptor, it is proposed the mentally retarded person becomes "addicted" to the reinforcing effects of these ligands which are released by self-injury. Since discontinuation of self- injury would induce an opiate-type abstinence syndrome, the mentally retarded person may (in part) continue to engage in self- injury to avoid withdrawal distress. Independent evidence shows clonidine diminishes opiate withdrawal symptoms in laboratory and clinical settings. It is proposed that naltrexone will block the reinforcing effect of the opioid ligand at the opiate receptor, and clonidine will diminish the tendency for the retarded individual to continue self-injuring to avoid opiate-like withdrawal. In the proposed research, standardized assessment instruments (Adaptive Behavior Scale, Part II; Aberrant Behavior Checklist) and direct observational techniques will be used. In addition to evaluating effects on self-injury, measures of other maladaptive behaviors and learning ability using a laboratory matching-to-sample procedure will be used.